Unique functional abnormalities in the lungs of HIV seropositive patients have recently been described. These abnormalities do not appear to be related to opportunistic infection and suggest an underlying process of alveolar capillary destruction occurring in association with HIV. Although this syndrome resembles emphysema, it has gone largely unrecognized, probably because of its atypical nature. However, it may be related to previously described but poorly understood HIV-associated pulmonary phenomena including diffusion impairment, exercise dysfunction, pulmonary hypertension, premature bullous disease and spontaneous pneumothorax. The underlying focus of the application is to clearly delineate this syndrome and carefully study its functional and morphologic characteristics. The specific aims of this application are as follows: (1) To test the hypothesis that there is a set of specific functional abnormalities of the lung associated with HIV infection which: 1) resemble an accelerated form of emphysema but are fundamentally different with respect to gas exchange and mechanics of breathing compared to other forms of "classic" emphysema, and 2) are not associated with the incidence of opportunistic infection but rather the severity and/or chronicity of HIV infection. Detailed studies of pulmonary function, including pulmonary mechanics, will be performed in HIV seropositive individuals in a longitudinal fashion. These results will be compared to control data as well as data obtained from a-1 antitrypsin deficient patients. Particular attention will be paid to the relationship between elastic recoil and air-flow obstruction. (2) To test the hypothesis that certain predisposing factors such as smoking history, method of exposure, nutritional status, and other influences are related to the incidence and/or the rate of decline in pulmonary function. In this specific aim, important aspects regarding contributing pathogenic factors will be explored. (3) To test the hypothesis that this HIV-associated pulmonary disease represents a form of predominant panlobular emphysema which is morphologically distinguishable from a-1 antitrypsin deficiency, smoking- induced emphysema and non-HIV-related opportunistic infection. Morphologic assessment will be made using high resolution computed tomography as well as direct histologic examination of autopsy and biopsy material. Important morphologic and functional correlates will be studied. This is a request for continuation of our previous application from two to five years. Given sufficient duration of support, we will be able to determine the functional and morphologic characteristics of this unusual disease process. Future studies will include the exploration of cellular and molecular mechanisms of parenchymal changes that will hopefully provide a window of opportunity for understanding general mechanisms of the emphysema process and the pathophysiology of HIV infection.